Connexin is a generic term for a family of membrane-associated proteins that form gap junctions. More than 12 subtypes of connexin have been found that are different in molecular weight from one another. Connexin with a molecular weight of 26 kDa is referred to as connexin 26, and with a molecular weight of 43 kDa it is referred to as connexin 43.
A hexamer of connexin is called a connexon. It forms a channel-like structure to penetrate cell membranes. A gap junction is formed of connexons connected to one another between adjacent cells. This connection results in the formation of a channel, through which ions and low molecular weight proteins are transferred from cell to cell. This mechanism is considered necessary, for example, to sustain the homeostatic growth of epithelial cells.
Through basic researches to find a cancer metastasis mechanism at a genetic level, the inventors of the present invention have found that connexin 26 is closely related to cancer metastasis, more specifically, the inhibition of a connexin 26 function inhibits cancer metastasis (Patent Document 1 and Nonpatent Document 1, described below).
The examples of known substances that inhibit gap junctions include oleamide, an amide derivative of oleic acid, and a derivative thereof (Nonpatent Document 2, described below). The present inventors identified the derivatives selected from oleamide derivatives that specifically inhibit connexin 26 and exhibit high cancer metastasis inhibitory activities. One was then named “MI-18” (Patent Document 2, described below).
Patent Documents 3 and 4, explained below, describe examples in which dimer oleamide derivatives are used as raw materials of imidazolidine. Also described is that the imidazolidine, which is a product, has an activity inhibiting the growth of, for example, bacteria and yeast in vitro.
[Patent Document 1] Japanese Laid-Open Patent Publication No. 2001-17184
[Patent Document 2] International Publication WO 2004/060398
[Patent Document 3] U.S. Pat. No. 3,872,120
[Patent Document 4] U.S. Pat. No. 3,875,159
[Nonpatent Document 1] Ito, A. et al.: J. Clin. Invest., 105:1189-1197, 2000
[Nonpatent Document 2] Boger, D. L. et al.: Proc. Nat. Acad. Sci. USA., 95:4810-4815. 1998)